The first section of this proposal deals with the total synthesis of codeine using a cationic cyclization route. 1-Acetamido-N-carbomethoxynordihydrothebainone has been synthesized and it is planned to convert this to 1-bromo-N-carbomethoxynordihydrothebainone an intermediate which will be transformed to codeine. We plan to study the conversion of 1-methyl-M-formyldihydrothebainone to dihydrothebainone dimethyl ketal, a substance which has been converted to codeine in high yield. The second section deals with the synthesis and biological evaluation of agonist and antagonist action, of a new series of 14-beta-substituted, N-substituted normorphine derivatives. Methods have been developed to introduce nitrogen, chlorine and sulfur at the 14-beta-position and we plan to use these methods and develop others to synthesize a variety of 14-beta-substituted N-methyl and N-cyclopropylmethyl morphine derivatives, with the intent of increasing potency and duration of antagonist action.